The present proposal is designed to provide further understanding of and insight into the pathogenesis, mode of transmission, and factors associated with activation and/or persistence of cytomegalovirus infection using guinea pigs and monkeys as animal models. These models are unique for study of species specific virus in its homologous host in that they possess certain physical attributes that render them comparable to the human virus-host relationship. Since the transplacental transmission of GPCMV in guinea pigs has now bee demonstrated, further studies will center on intrauterine infection, with special emphasis on obtaining evidence of neurologic sequelae in newborns. Host response to CMV infection in guinea pigs has not been previously explored; the proposal includes experiments for the determination of both viral persistency in a particular cell type and effect of virus infection on cell mediated immune mechanism. Finally, studies will be carried out in an effort to assess the potential than an attenuated or subunit GPCMV vaccine has for protecting guinea pigs, especially the fetuses, from the consequences of GPCMV infection by conferring active immunity as the result of vaccination. The data obtained in these sudies should be particularly useful in their application to the problems associated with human CMV infection and pathogenesis.